Joseph Ventura

Training and quality assurance with the structured clinical interview for DSM-IV (SCID-I/P)

Accuracy in psychiatric diagnosis is critical for evaluating the suitability of the subjects for entry into research protocols and for establishing comparability of findings across study sites. However, training programs in the use of diagnostic instruments for research projects are not well systematized. Furthermore, little information has been published on the maintenance of interrater reliability of diagnostic assessments. At the UCLA Research Center for Major Mental Illnesses, a Training and Quality Assurance Program for SCID interviewers was used to evaluate interrater reliability and diagnostic accuracy. Although clinically experienced interviewers achieved better interrater reliability and overall diagnostic accuracy than neophyte interviewers, both groups were able to achieve and maintain high levels of interrater reliability, diagnostic accuracy, and interviewer skill. At the first quality assurance check after training, there were no significant differences between experienced and neophyte interviewers in interrater reliability or diagnostic accuracy. Standardization of training and quality assurance procedures within and across research projects may make research findings from study sites more comparable.

Operational criteria and factors related to recovery from schizophrenia

Schizophrenia is often conceptualized by clinicians and researchers alike as a chronic illness with persisting, relapsing or deteriorating symptoms, and no hope for sustained remission and recovery of functioning. Countering this perspective, retrospective and prospective studies with both chronic and recent onset patients suggest that schizophrenia has a heterogeneous course, which can be favorably influenced by comprehensive and continuous treatment as well as personal factors such as family support and good neurocognitive functioning. The factors influencing recovery are mostly malleable through treatment and may often lead to a sustained remission of symptoms and normal or near-normal levels of functioning.To facilitate future research in this area, an operational definition of recovery from schizophrenia is proposed that includes symptom remission; full- or part-time involvement in work or school; independent living without supervision by family or surrogate caregivers; not fully dependent on financial support from disability insurance; and having friends with whom activities are shared on a regular basis. To satisfy the definition of recovery from the long-term illness of schizophrenia, each of the above criteria should be sustained for at least two consecutive years. For validation, these criteria were submitted to focus groups comprising clients, family members, practitioners, and researchers. Using this operational definition, a pilot study was conducted to identify the self-attributions, clinical characteristics and neurocognitive correlates of 23 individuals who have recovered from schizophrenia. The focus groups endorsed most of the criteria as being relevant to the construct of recovery, although there were differences between research investigators and others. The pilot study generated hypotheses for future testing, suggesting that quality of sustained treatment, near-normal neurocognition, and absence of the deficit syndrome were key factors associated with recovery. With operational definitions and variables identified as possible facilitators of recovery, both hypothesis-generating and testing research can proceed with the aim to identify factors that are malleable and can become targets for therapeutic intervention. There are many extant, evidence-based biobehavioral treatments, as well as mental health service systems for their delivery, that could form the basis for rapid progress in promoting recovery. However, obstacles would have to be overcome to the dissemination, re-invention and utilization of empirically validated treatments, while rigorous, controlled research on determinants of recovery are simultaneously begun.

Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: A meta-analysis

BACKGROUND Neurocognitive functioning in schizophrenia has received considerable attention because of its robust prediction of functional outcome. Psychiatric symptoms, in particular negative symptoms, have also been shown to predict functional outcome, but have garnered much less attention. The high degree of intercorrelation among all of these variables leaves unclear whether neurocognition has a direct effect on functional outcome or whether that relationship to functional outcome is partially mediated by symptoms. METHODS A meta-analysis of 73 published English language studies (total n=6519) was conducted to determine the magnitude of the relationship between neurocognition and symptoms, and between symptoms and functional outcome. A model was tested in which symptoms mediate the relationship between neurocognition and functional outcome. Functional outcome involved measures of social relationships, school and work functioning, and laboratory assessments of social skill. RESULTS Although negative symptoms were found to be significantly related to neurocognitive functioning (p<.01) positive symptoms were not (p=.97). The relationship was moderate for negative symptoms (r=-.24, n=4757, 53 studies), but positive symptoms were not at all related to neurocogniton (r=.00, n=1297, 25 studies). Negative symptoms were significantly correlated with functional outcome (r=-.42, p<.01), and again the correlation was higher than for positive symptoms (r=-.03, p=.55). Furthermore, our findings support a model in which negative symptoms significantly mediate the relationship between neurocognition and functional outcome (Sobel test p<.01). CONCLUSIONS Although neurocognition and negative symptoms are both predictors of functional outcome, negative symptoms might at least partially mediate the relationship between neurocognition and outcome.

Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale

Previous four- and five-factor solutions of the 18-item Brief Psychiatric Rating Scale (BPRS) suggested the possibility of an affective dimension in psychosis. A principal components analysis was used to analyze psychiatric symptom data rated on an expanded 24-item version of the BPRS. BPRS data were collected during a period of acute psychotic and affective illness with 114 young adult, recent-onset schizophrenia and schizoaffective patients and 27 bipolar manic patients. Principal components analyses of the 18-item and 24-item BPRS indicated a four-factor solution was the most interpretable. Principal components analysis of the 24-item BPRS produced a clear mania factor characterized by high loadings from items added to the 18-item BPRS, which included elevated mood, motor hyperactivity, and distractibility. This factor solution suggests that the 24-item BPRS allows for an expanded assessment of affective symptoms relating to a manic dimension. Potentially important symptoms that were added to the traditional 18-item version, namely suicidality, bizarre behavior, and self-neglect, also make clear contributions to other factors.

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects

BACKGROUND Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.

Social Cognition in Schizophrenia, Part 1: Performance Across Phase of Illness

Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample.

The vulnerability/stress model of schizophrenic relapse: a longitudinal study

A tentative model for conceptualizing the interplay of vulnerability factors, stressors, and protective factors in the course of schizophrenia is discussed. A study of the initial years after a first schizophrenic episode is testing the predictive role of key factors. During an initial 1‐year period of depot antipsychotic medication, independent life events and expressed emotion were found to predict the likelihood of psychotic relapse. Initial analyses indicate that independent life events play less of a role in relapse prediction during a medication‐free period. These results suggest that maintenance antipsychotic medication raises the threshold for return of psychotic symptoms, such that relapses are less likely unless major environmental stressors occur. A low expressed emotion environment may be a protective factor.

Social Cognition in Schizophrenia, Part 2: 12-Month Stability and Prediction of Functional Outcome in First-Episode Patients

This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets.

Neurocognitive predictors of work outcome in recent-onset schizophrenia.

While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.

Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression

Proton magnetic resonance spectroscopy (1HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR=30/3000 ms, 3 × 3 × 3 cm3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate+glutamine ([Glx]), glutamate ([Glu]), and creatine+phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.